 David Julius, PhD
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| Title | Professor |
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| School | UCSF School of Medicine |
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| Department | Physiology |
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| Address | GH 600 16th Street
SAN FRANCISCO CA 94158
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| Phone | 415-476-0431 |
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 Overview My group is interested in understanding how signals are received and transmitted by the nervous system. In one aspect of our research, we have exploited the power of natural products to elucidate molecular mechanisms of touch and pain sensation. For example, we have asked how capsaicin, the main pungent ingredient in "hot" chili peppers, elicits burning pain, and how menthol, the cooling agent in mint leaves, evokes an icy cool sensation. Using these agents as pharmacological probes, we have identified ion channels on sensory nerve fibers that are activated by heat or cold, providing molecular insight into the process of thermosensation. With the aid of genetic, electrophysiological, and behavioral methods, we are asking how these ion channels contribute to the detection of heat or cold, and how their activity is modulated in response to tumor growth, infection, or other forms of injury that produce inflammation and pain hypersensitivity.
In addition to our work on somatosensation and pain, we also study the structure and function of specific neurotransmitter receptors, such as those activated by serotonin or extracellular nucleotides, and use genetic methods to identify roles for these receptors in physiological and behavioral processes, such as feeding, anxiety, pain, thrombosis, and cell growth and motility.
Bibliographic
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications.
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Cao E, Cordero-Morales JF, Liu B, Qin F, Julius D. TRPV1 Channels Are Intrinsically Heat Sensitive and Negatively Regulated by Phosphoinositide Lipids. Neuron. 2013 Feb 20; 77(4):667-79.
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Bohlen CJ, Julius D. Receptor-targeting mechanisms of pain-causing toxins: How ow? Toxicon. 2012 Sep 1; 60(3):254-64.
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Julius D, Nathans J. Signaling by sensory receptors. Cold Spring Harb Perspect Biol. 2012 Jan; 4(1):a005991.
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Bohlen CJ, Chesler AT, Sharif-Naeini R, Medzihradszky KF, Zhou S, King D, Sánchez EE, Burlingame AL, Basbaum AI, Julius D. A heteromeric Texas coral snake toxin targets acid-sensing ion channels to produce pain. Nature. 2011 Nov 17; 479(7373):410-4.
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Cordero-Morales JF, Gracheva EO, Julius D. Cytoplasmic ankyrin repeats of transient receptor potential A1 (TRPA1) dictate sensitivity to thermal and chemical stimuli. Proc Natl Acad Sci U S A. 2011 Nov 15; 108(46):E1184-91.
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Gracheva EO, Cordero-Morales JF, González-Carcacía JA, Ingolia NT, Manno C, Aranguren CI, Weissman JS, Julius D. Ganglion-specific splicing of TRPV1 underlies infrared sensation in vampire bats. Nature. 2011 Aug 4; 476(7358):88-91.
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Cavanaugh DJ, Chesler AT, Bráz JM, Shah NM, Julius D, Basbaum AI. Restriction of transient receptor potential vanilloid-1 to the peptidergic subset of primary afferent neurons follows its developmental downregulation in nonpeptidergic neurons. J Neurosci. 2011 Jul 13; 31(28):10119-27.
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Cavanaugh DJ, Chesler AT, Jackson AC, Sigal YM, Yamanaka H, Grant R, O'Donnell D, Nicoll RA, Shah NM, Julius D, Basbaum AI. Trpv1 reporter mice reveal highly restricted brain distribution and functional expression in arteriolar smooth muscle cells. J Neurosci. 2011 Mar 30; 31(13):5067-77.
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Bohlen CJ, Priel A, Zhou S, King D, Siemens J, Julius D. A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain. Cell. 2010 May 28; 141(5):834-45.
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Gracheva EO, Ingolia NT, Kelly YM, Cordero-Morales JF, Hollopeter G, Chesler AT, Sánchez EE, Perez JC, Weissman JS, Julius D. Molecular basis of infrared detection by snakes. Nature. 2010 Apr 15; 464(7291):1006-11.
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Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell. 2009 Oct 16; 139(2):267-84.
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Myers BR, Sigal YM, Julius D. Evolution of thermal response properties in a cold-activated TRP channel. PLoS One. 2009; 4(5):e5741.
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Bhattacharya MR, Bautista DM, Wu K, Haeberle H, Lumpkin EA, Julius D. Radial stretch reveals distinct populations of mechanosensitive mammalian somatosensory neurons. Proc Natl Acad Sci U S A. 2008 Dec 16; 105(50):20015-20.
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Myers BR, Saimi Y, Julius D, Kung C. Multiple unbiased prospective screens identify TRP channels and their conserved gating elements. J Gen Physiol. 2008 Nov; 132(5):481-6.
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Prober DA, Zimmerman S, Myers BR, McDermott BM, Kim SH, Caron S, Rihel J, Solnica-Krezel L, Julius D, Hudspeth AJ, Schier AF. Zebrafish TRPA1 channels are required for chemosensation but not for thermosensation or mechanosensory hair cell function. J Neurosci. 2008 Oct 1; 28(40):10102-10.
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Bautista DM, Sigal YM, Milstein AD, Garrison JL, Zorn JA, Tsuruda PR, Nicoll RA, Julius D. Pungent agents from Szechuan peppers excite sensory neurons by inhibiting two-pore potassium channels. Nat Neurosci. 2008 Jul; 11(7):772-9.
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Myers BR, Bohlen CJ, Julius D. A yeast genetic screen reveals a critical role for the pore helix domain in TRP channel gating. Neuron. 2008 May 8; 58(3):362-73.
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Bautista D, Julius D. Fire in the hole: pore dilation of the capsaicin receptor TRPV1. Nat Neurosci. 2008 May; 11(5):528-9.
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McNamara CR, Mandel-Brehm J, Bautista DM, Siemens J, Deranian KL, Zhao M, Hayward NJ, Chong JA, Julius D, Moran MM, Fanger CM. TRPA1 mediates formalin-induced pain. Proc Natl Acad Sci U S A. 2007 Aug 14; 104(33):13525-30.
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Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, Imamachi N, Andrè E, Patacchini R, Cottrell GS, Gatti R, Basbaum AI, Bunnett NW, Julius D, Geppetti P. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A. 2007 Aug 14; 104(33):13519-24.
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Myers BR, Julius D. TRP channel structural biology: new roles for an old fold. Neuron. 2007 Jun 21; 54(6):847-50.
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Bautista DM, Siemens J, Glazer JM, Tsuruda PR, Basbaum AI, Stucky CL, Jordt SE, Julius D. The menthol receptor TRPM8 is the principal detector of environmental cold. Nature. 2007 Jul 12; 448(7150):204-8.
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Kayser V, Elfassi IE, Aubel B, Melfort M, Julius D, Gingrich JA, Hamon M, Bourgoin S. Mechanical, thermal and formalin-induced nociception is differentially altered in 5-HT1A-/-, 5-HT1B-/-, 5-HT2A-/-, 5-HT3A-/- and 5-HTT-/- knock-out male mice. Pain. 2007 Aug; 130(3):235-48.
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Hinman A, Chuang HH, Bautista DM, Julius D. TRP channel activation by reversible covalent modification. Proc Natl Acad Sci U S A. 2006 Dec 19; 103(51):19564-8.
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Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci. 2006 Dec; 9(12):1512-9.
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Siemens J, Zhou S, Piskorowski R, Nikai T, Lumpkin EA, Basbaum AI, King D, Julius D. Spider toxins activate the capsaicin receptor to produce inflammatory pain. Nature. 2006 Nov 9; 444(7116):208-12.
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Eckert WA, Julius D, Basbaum AI. Differential contribution of TRPV1 to thermal responses and tissue injury-induced sensitization of dorsal horn neurons in laminae I and V in the mouse. Pain. 2006 Dec 15; 126(1-3):184-97.
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Tsuruda PR, Julius D, Minor DL. Coiled coils direct assembly of a cold-activated TRP channel. Neuron. 2006 Jul 20; 51(2):201-12.
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Marasco PD, Tsuruda PR, Bautista DM, Julius D, Catania KC. Neuroanatomical evidence for segregation of nerve fibers conveying light touch and pain sensation in Eimer's organ of the mole. Proc Natl Acad Sci U S A. 2006 Jun 13; 103(24):9339-44.
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Basbaum AI, Julius D. Toward better pain control. Sci Am. 2006 Jun; 294(6):60-7.
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Bautista DM, Jordt SE, Nikai T, Tsuruda PR, Read AJ, Poblete J, Yamoah EN, Basbaum AI, Julius D. TRPA1 mediates the inflammatory actions of environmental irritants and proalgesic agents. Cell. 2006 Mar 24; 124(6):1269-82.
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Clapham DE, Julius D, Montell C, Schultz G. International Union of Pharmacology. XLIX. Nomenclature and structure-function relationships of transient receptor potential channels. Pharmacol Rev. 2005 Dec; 57(4):427-50.
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Julius D, Basbaum AI. A neuropeptide courier for delta-opioid receptors? Cell. 2005 Aug 26; 122(4):496-8.
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Bautista DM, Movahed P, Hinman A, Axelsson HE, Sterner O, Högestätt ED, Julius D, Jordt SE, Zygmunt PM. Pungent products from garlic activate the sensory ion channel TRPA1. Proc Natl Acad Sci U S A. 2005 Aug 23; 102(34):12248-52.
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Ghilardi JR, Röhrich H, Lindsay TH, Sevcik MA, Schwei MJ, Kubota K, Halvorson KG, Poblete J, Chaplan SR, Dubin AE, Carruthers NI, Swanson D, Kuskowski M, Flores CM, Julius D, Mantyh PW. Selective blockade of the capsaicin receptor TRPV1 attenuates bone cancer pain. J Neurosci. 2005 Mar 23; 25(12):3126-31.
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Julius D. From peppers to peppermints: natural products as probes of the pain pathway. Harvey Lect. 2005-2006; 101:89-115.
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Julius D, Katz LC. A Nobel for smell. Cell. 2004 Dec 17; 119(6):747-52.
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Chuang HH, Neuhausser WM, Julius D. The super-cooling agent icilin reveals a mechanism of coincidence detection by a temperature-sensitive TRP channel. Neuron. 2004 Sep 16; 43(6):859-69.
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Bhattacharya A, Dang H, Zhu QM, Schnegelsberg B, Rozengurt N, Cain G, Prantil R, Vorp DA, Guy N, Julius D, Ford AP, Lester HA, Cockayne DA. Uropathic observations in mice expressing a constitutively active point mutation in the 5-HT3A receptor subunit. J Neurosci. 2004 Jun 16; 24(24):5537-48.
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Bhatnagar S, Sun LM, Raber J, Maren S, Julius D, Dallman MF. Changes in anxiety-related behaviors and hypothalamic-pituitary-adrenal activity in mice lacking the 5-HT-3A receptor. Physiol Behav. 2004 Jun; 81(4):545-55.
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Sanderson Nydahl K, Skinner K, Julius D, Basbaum AI. Co-localization of endomorphin-2 and substance P in primary afferent nociceptors and effects of injury: a light and electron microscopic study in the rat. Eur J Neurosci. 2004 Apr; 19(7):1789-99.
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Lewinter RD, Skinner K, Julius D, Basbaum AI. Immunoreactive TRPV-2 (VRL-1), a capsaicin receptor homolog, in the spinal cord of the rat. J Comp Neurol. 2004 Mar 15; 470(4):400-8.
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Jordt SE, Bautista DM, Chuang HH, McKemy DD, Zygmunt PM, Högestätt ED, Meng ID, Julius D. Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1. Nature. 2004 Jan 15; 427(6971):260-5.
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Clapham DE, Montell C, Schultz G, Julius D. International Union of Pharmacology. XLIII. Compendium of voltage-gated ion channels: transient receptor potential channels. Pharmacol Rev. 2003 Dec; 55(4):591-6.
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Jordt SE, McKemy DD, Julius D. Lessons from peppers and peppermint: the molecular logic of thermosensation. Curr Opin Neurobiol. 2003 Aug; 13(4):487-92.
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Prescott ED, Julius D. A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science. 2003 May 23; 300(5623):1284-8.
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McKemy DD, Neuhausser WM, Julius D. Identification of a cold receptor reveals a general role for TRP channels in thermosensation. Nature. 2002 Mar 7; 416(6876):52-8.
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Jordt SE, Julius D. Molecular basis for species-specific sensitivity to "hot" chili peppers. Cell. 2002 Feb 8; 108(3):421-30.
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Montell C, Birnbaumer L, Flockerzi V, Bindels RJ, Bruford EA, Caterina MJ, Clapham DE, Harteneck C, Heller S, Julius D, Kojima I, Mori Y, Penner R, Prawitt D, Scharenberg AM, Schultz G, Shimizu N, Zhu MX. A unified nomenclature for the superfamily of TRP cation channels. Mol Cell. 2002 Feb; 9(2):229-31.
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Zeitz KP, Guy N, Malmberg AB, Dirajlal S, Martin WJ, Sun L, Bonhaus DW, Stucky CL, Julius D, Basbaum AI. The 5-HT3 subtype of serotonin receptor contributes to nociceptive processing via a novel subset of myelinated and unmyelinated nociceptors. J Neurosci. 2002 Feb 1; 22(3):1010-9.
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Julius D, Basbaum AI. Molecular mechanisms of nociception. Nature. 2001 Sep 13; 413(6852):203-10.
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McNamara N, Khong A, McKemy D, Caterina M, Boyer J, Julius D, Basbaum C. ATP transduces signals from ASGM1, a glycolipid that functions as a bacterial receptor. Proc Natl Acad Sci U S A. 2001 Jul 31; 98(16):9086-91.
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Chuang HH, Prescott ED, Kong H, Shields S, Jordt SE, Basbaum AI, Chao MV, Julius D. Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition. Nature. 2001 Jun 21; 411(6840):957-62.
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Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature. 2001 Jan 11; 409(6817):202-7.
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Caterina MJ, Julius D. The vanilloid receptor: a molecular gateway to the pain pathway. Annu Rev Neurosci. 2001; 24:487-517.
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Jordt SE, Tominaga M, Julius D. Acid potentiation of the capsaicin receptor determined by a key extracellular site. Proc Natl Acad Sci U S A. 2000 Jul 5; 97(14):8134-9.
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Tominaga M, Julius D. Capsaicin receptor in the pain pathway. Jpn J Pharmacol. 2000 May; 83(1):20-4.
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Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, Koltzenburg M, Basbaum AI, Julius D. Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science. 2000 Apr 14; 288(5464):306-13.
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Caterina MJ, Julius D. Sense and specificity: a molecular identity for nociceptors. Curr Opin Neurobiol. 1999 Oct; 9(5):525-30.
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Melck D, Bisogno T, De Petrocellis L, Chuang H, Julius D, Bifulco M, Di Marzo V. Unsaturated long-chain N-acyl-vanillyl-amides (N-AVAMs): vanilloid receptor ligands that inhibit anandamide-facilitated transport and bind to CB1 cannabinoid receptors. Biochem Biophys Res Commun. 1999 Aug 19; 262(1):275-84.
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Zygmunt PM, Petersson J, Andersson DA, Chuang H, Sørgård M, Di Marzo V, Julius D, Högestätt ED. Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide. Nature. 1999 Jul 29; 400(6743):452-7.
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Caterina MJ, Rosen TA, Tominaga M, Brake AJ, Julius D. A capsaicin-receptor homologue with a high threshold for noxious heat. Nature. 1999 Apr 1; 398(6726):436-41.
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Julius D. Serotonin receptor knockouts: a moody subject. Proc Natl Acad Sci U S A. 1998 Dec 22; 95(26):15153-4.
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Tominaga M, Caterina MJ, Malmberg AB, Rosen TA, Gilbert H, Skinner K, Raumann BE, Basbaum AI, Julius D. The cloned capsaicin receptor integrates multiple pain-producing stimuli. Neuron. 1998 Sep; 21(3):531-43.
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Bedford FK, Julius D, Ingraham HA. Neuronal expression of the 5HT3 serotonin receptor gene requires nuclear factor 1 complexes. J Neurosci. 1998 Aug 15; 18(16):6186-94.
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England LJ, Imperial J, Jacobsen R, Craig AG, Gulyas J, Akhtar M, Rivier J, Julius D, Olivera BM. Inactivation of a serotonin-gated ion channel by a polypeptide toxin from marine snails. Science. 1998 Jul 24; 281(5376):575-8.
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Caterina MJ, Schumacher MA, Tominaga M, Rosen TA, Levine JD, Julius D. The capsaicin receptor: a heat-activated ion channel in the pain pathway. Nature. 1997 Oct 23; 389(6653):816-24.
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Brake A, Schumacher M, Julius D. ATP receptors in sickness, pain and death. Chem Biol. 1996 Apr; 3(4):229-32.
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Brake AJ, Julius D. Signaling by extracellular nucleotides. Annu Rev Cell Dev Biol. 1996; 12:519-41.
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Bedford FK, Christopherson K, Nachtigal MW, Shen WH, Julius DJ, Ingraham HA. Molecular biology of pituitary development and disease. Horm Res. 1996; 45 Suppl 1:19-21.
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Julius D. Pharmacology. Home for an orphan endorphin. Nature. 1995 Oct 12; 377(6549):476.
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Tecott LH, Sun LM, Akana SF, Strack AM, Lowenstein DH, Dallman MF, Julius D. Eating disorder and epilepsy in mice lacking 5-HT2c serotonin receptors. Nature. 1995 Apr 6; 374(6522):542-6.
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Tecott L, Shtrom S, Julius D. Expression of a serotonin-gated ion channel in embryonic neural and nonneural tissues. Mol Cell Neurosci. 1995 Feb; 6(1):43-55.
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Brake AJ, Wagenbach MJ, Julius D. New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature. 1994 Oct 6; 371(6497):519-23.
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Lustig KD, Shiau AK, Brake AJ, Julius D. Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc Natl Acad Sci U S A. 1993 Jun 1; 90(11):5113-7.
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Tecott LH, Julius D. A new wave of serotonin receptors. Curr Opin Neurobiol. 1993 Jun; 3(3):310-5.
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Conklin BR, Farfel Z, Lustig KD, Julius D, Bourne HR. Substitution of three amino acids switches receptor specificity of Gq alpha to that of Gi alpha. Nature. 1993 May 20; 363(6426):274-6.
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Tecott LH, Maricq AV, Julius D. Nervous system distribution of the serotonin 5-HT3 receptor mRNA. Proc Natl Acad Sci U S A. 1993 Feb 15; 90(4):1430-4.
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Milatovich A, Hsieh CL, Bonaminio G, Tecott L, Julius D, Francke U. Serotonin receptor 1c gene assigned to X chromosome in human (band q24) and mouse (bands D-F4). Hum Mol Genet. 1992 Dec; 1(9):681-4.
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Kahan C, Julius D, Pouysségur J, Seuwen K. Effects of 5-HT1C-receptor expression on cell proliferation control in hamster fibroblasts: serotonin fails to induce a transformed phenotype. Exp Cell Res. 1992 Jun; 200(2):523-7.
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Maricq AV, Peterson AS, Brake AJ, Myers RM, Julius D. Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science. 1991 Oct 18; 254(5030):432-7.
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Julius D. Molecular biology of serotonin receptors. Annu Rev Neurosci. 1991; 14:335-60.
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Hsieh CL, Bowcock AM, Farrer LA, Hebert JM, Huang KN, Cavalli-Sforza LL, Julius D, Francke U. The serotonin receptor subtype 2 locus HTR2 is on human chromosome 13 near genes for esterase D and retinoblastoma-1 and on mouse chromosome 14. Somat Cell Mol Genet. 1990 Nov; 16(6):567-74.
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Julius D, Huang KN, Livelli TJ, Axel R, Jessell TM. The 5HT2 receptor defines a family of structurally distinct but functionally conserved serotonin receptors. Proc Natl Acad Sci U S A. 1990 Feb; 87(3):928-32.
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Molineaux SM, Jessell TM, Axel R, Julius D. 5-HT1c receptor is a prominent serotonin receptor subtype in the central nervous system. Proc Natl Acad Sci U S A. 1989 Sep; 86(17):6793-7.
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Julius D, Livelli TJ, Jessell TM, Axel R. Ectopic expression of the serotonin 1c receptor and the triggering of malignant transformation. Science. 1989 Jun 2; 244(4908):1057-62.
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Julius D, MacDermott AB, Axel R, Jessell TM. Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science. 1988 Jul 29; 241(4865):558-64.
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Julius D, MacDermott AB, Jessel TM, Huang K, Molineaux S, Schieren I, Axel R. Functional expression of the 5-HT1c receptor in neuronal and nonneuronal cells. Cold Spring Harb Symp Quant Biol. 1988; 53 Pt 1:385-93.
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Julius D, Brake A, Blair L, Kunisawa R, Thorner J. Isolation of the putative structural gene for the lysine-arginine-cleaving endopeptidase required for processing of yeast prepro-alpha-factor. Cell. 1984 Jul; 37(3):1075-89.
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Julius D, Schekman R, Thorner J. Glycosylation and processing of prepro-alpha-factor through the yeast secretory pathway. Cell. 1984 Feb; 36(2):309-18.
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Brake AJ, Julius DJ, Thorner J. A functional prepro-alpha-factor gene in Saccharomyces yeasts can contain three, four, or five repeats of the mature pheromone sequence. Mol Cell Biol. 1983 Aug; 3(8):1440-50.
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Julius D, Blair L, Brake A, Sprague G, Thorner J. Yeast alpha factor is processed from a larger precursor polypeptide: the essential role of a membrane-bound dipeptidyl aminopeptidase. Cell. 1983 Mar; 32(3):839-52.
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Goldberg SC, Shenoy RS, Julius D, Hamer RM, Ross B, Minton T, Spiro M. Does long-acting injectable neuroleptic protect against tardive dyskinesia? Psychopharmacol Bull. 1982 Oct; 18(4):177-9.
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Julius DJ, Fraser TH, Rich A. Isomeric specificity of aminoacylation of wheat germ transfer ribonucleic acid and the specificity of interaction of elongation factor Tu with aminoacyl transfer ribonucleic acid. Biochemistry. 1979 Feb 20; 18(4):604-9.
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Fraser TH, Julius DJ, Rich A. Determination of aminoacylation isomeric specificity using tRNA terminating in 3'-amino-3'-deoxyadenosine and 2'-amino-2'-deoxyadenosine. Methods Enzymol. 1979; 59:272-82.
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